Pharmaceutical cocrystals is an advanced technology to improve the physicochemical and biological properties of drugs. However, there are few studies on the in vivo metabolism of pharmaceutical cocrystals. In this study, the pharmacokinetics of wogonin cocrystal in normal rats was further studied on the basis of the previous preparation of wogonin-aloperine cocrystal. Firstly, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for simultaneous determination of wogonin and its metabolite wogonoside in rat plasma, and to investigate the methodology. The method was applied to the pharmacokinetic study of wogonin-aloperine cocrystal (Wog-Alop) in rats. The results showed that wogonin and its metabolite wogonoside had a good linear relationship in the range of 1-800 ng·mL^-1, and the precision, accuracy, matrix effect and stability in this range met the requirements of biological analysis. Compared with direct administration of wogonin, the C_max of wogonin and its metabolite in rats increased to 7.44-fold and 9.15-fold, AUC_0-t increased to 1.67-fold and 3.72-fold, and oral bioavailability of wogonin increased to 187.66% after cocrystal administration. Wog-Alop cocrystal can significantly improve the C_max, AUC, and oral bioavailability of wogonin and its metabolite, which provides a new perspective for the clinical application of wogonin. This study was approved by the Experimental Animal Ethics Review Committee of Beijing University of Chinese Medicine (approval number: BUCM-2023032307-1148).

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective:To investigate the current situation of the " Internet plus nursing services" for the elderly in Ningbo, and evaluate the promotion effect of the pilot policy, for reference to further optimize such service policy of China nationwide.Methods:The data came from the orders for " Internet plus nursing services" by elderly users over 60 years on the " cloud hospital" platform in Ningbo from 2016 to 2021. Descriptive analysis was used to study major demographic information, types of service items and number of person-times of the elderly users; The promotion effect of the pilot policy on " Internet plus nursing services" for the elderly in 2019 was analysed by Chow test.Results:The number of elderly users increased from 76 person-times in 2016 to 5 923 person-times in 2021, accumulating up to 12 209 person-times. The number of nursing service items increased from 18 in 2016 to 36 in 2021. The person-times of users of common clinical nursing and specialized nursing service items were 11 850 and 359 respectively. After the pilot policy was issued, the number of service items and the number of users were significantly increased in 2020( P<0.05). Conclusions:The development of " Internet plus nursing services" for the elderly in Ningbo had achieved certain results, especially with the promotion of the pilot policy in 2019, the types of service items and the number of elderly users had increased year by year. In the future, we should continue to focus on the elderly living alone and other special elderly groups with the support of relevant policies, further expand the scale of elderly users, improve the types of service items, and optimize the charging standards to help China′s healthy aging process.

AIM:To investigate the effects of platelet-derived growth factor receptor α(PDGFRα) on melano-cyte apoptosis induced by hydrogen peroxide(H2O2). METHODS:Melanocyte PIGI was used as the research object. Af-ter exposed to H2O2at different concentrations,the cell viability was detected by MTT assay. The PIGI cells were transfec-ted with empty vector pCMV6 or PDGFRα over-expression vector pCMV6-PDGFRα. The transfection efficiency was deter-mined by RT-qPCR and Western blot. The effect of H2O2on the viability of the PIGI cells after over-expression of PDGFRα was measured by MTT assay. The cell apoptosis was analyzed by flow cytometry. The protein levels of p38, p-p38 and cleaved caspase-3 in the cells were detected by Western blot. DCDHF-DA was used to estemate the generation of reactive oxygen species (ROS) in the cells. RESULTS:The viability of PIGI cells decreased after exposed to H2O2(P<0.05), and the half maximal inhibitory concentration of H2O2was 0.7 mmol/L. Transfection with PDGFRα over-expression vector successfully induced high expression of PDGFRα at mRNA and protein levels in the PIGI cells,and increased the viability of the cells with H2O2treatment(P<0.05). Over-expression of PDGFRα decreased the apoptotic rate of PIGI cells trea-ted with H2O2(P<0.05),and the level of ROS in the cells(P<0.05). The protein levels of cleaved caspase-3 and p-p38 were also decreased (P <0.05). CONCLUSION:PDGFRα inhibits the apoptosis of melanocytes induced by H2O2,partially reverses the growth inhibition of melanocytes by H2O2,and decreases the ROS level. The mechanism may be related to regulating the protein levels of p-p38 and cleaved caspase-3 in the cells.

Follicle-stimulating hormone (FSH) is synthesized and secreted by the anterior pituitary, which binds to its receptors expressed on the membrane of Sertoli cells in the testis to bring about spermatogenesis. With the development of DNA sequencing technology, FSH SNPs rs10835638 and FSHR SNPs rs6165, rs6166, and rs1394205 were detected, which might directly affect the expression of FSH and activity of FSHR, resulting in male spermatogenic dysfunction. This review focuses on the relationship of FSH and FSHR gene polymorphisms with male infertility.
Follicle Stimulating Hormone ; genetics ; Humans ; Infertility, Male ; genetics ; Male ; Polymorphism, Single Nucleotide ; Receptors, FSH ; genetics ; Sertoli Cells ; Spermatogenesis ; Testis

OBJECTIVETo compare the efficacy difference in the treatment of shoulder pain in post-stroke shoulder-hand syndrome among floating acupuncture, oral administration of western medicine and local fumigation of Chinese herbs.

METHODSNinety cases of post-stroke shoulder-hand syndrome (stage I) were randomized into a floating acupuncture group, a western medicine group and a local Chinese herbs fumigation group, 30 cases in each one. In the floating acupuncture group, two obvious tender points were detected on the shoulder and the site 80-100 mm inferior to each tender point was taken as the inserting point and stimulated with floating needling technique. In the western medicine group, mobic 7.5 mg was prescribed for oral administration. In the local Chinese herbs fumigation group, the formula for activating blood circulation and relaxing tendon was used for local fumigation. All the patients in three groups received rehabilitation training. The floating acupuncture, oral administration of western medicine, local Chinese herbs fumigation and rehabilitation training were given once a day respectively in corresponding group and the cases were observed for 1 month. The visual analogue scale (VAS) and Takagishi shoulder joint function assessment were adopted to evaluate the dynamic change of the patients with shoulder pain before and after treatment in three groups. The modified Barthel index was used to evaluate the dynamic change of daily life activity of the patients in three groups.

RESULTSWith floating acupuncture, shoulder pain was relieved and the daily life activity was improved in the patients with post-stroke shoulder-hand syndrome, which was superior to the oral administration of western medicine and local Chinese herbs fumigation (P < 0.01). With local Chinese herbs fumigation, the improvement of shoulder pain was superior to the oral administration of western medicine. The difference in the improvement of daily life activity was not significant statistically between the local Chinese herbs fumigation and oral administration of western medicine, the efficacy was similar between these two therapies (P > 0.05).

CONCLUSIONThe floating acupuncture relieves shoulder pain of the patients with post-stroke shoulder-hand syndrome promptly and effectively, and the effects on shoulder pain and the improvements of daily life activity are superior to that of the oral administration of western medicine and local Chinese herbs fumigation.

Acupuncture Therapy ; Aged ; Female ; Humans ; Male ; Middle Aged ; Reflex Sympathetic Dystrophy ; etiology ; rehabilitation ; therapy ; Shoulder Pain ; etiology ; rehabilitation ; therapy ; Stroke ; complications ; Treatment Outcome

OBJECTIVETo assess the level of dietary iodine intake and its contribution in Zhejiang.

METHODSA total of 9798 subjects were recruited in this survey with multi-stage stratified cluster random sampling method in April, 2010, the 24-hours dietary recall method and the "food composition table" were used to obtain the dietary iodine intake, and edible salt and drinking water samples were collected to detect the content of iodine.

RESULTSA total of 9798 subjects were included in this survey. The mean intake of dietary iodine in Zhejiang residents per standard man-days was (395.13 ± 78.16) µg/d, which in between of Recommended Nutrient Intake (RNI) 150 µg/d and Tolerable Upper Intake Level (UL) 1000 µg/d; the iodine intake of 18.40% (1803/9798) subjects was lower than estimated average requirement of iodine (EAR), 4.68% (459/9798) subjects was higher than the UL. The means of dietary iodine intake in various areas were (498.85 ± 96.77) µg/d, (384.50 ± 88.76) µg/d and (326.33 ± 78.32)µg/d in inland areas, sub-coastal areas and coastal areas, successively (F = 27.17, P < 0.05); the proportions of dietary iodine intake lower than EAR were 34.89% (1239/3551), 10.48% (370/3530) and 7.14% (197/2717) in coastal areas, sub-coastal area and inland areas, successively (χ(2) = 62.87, P < 0.01) , while those higher than UL were 5.10% (180/3530), 4.86% (132/2717) and 4.14% (147/3551) in sub-coastal area, inland areas and coastal areas.In the condition of ignoring cooking loss, the mean contribution of dietary iodine intake in edible salt, all kinds of food and drinking water were 74.92% (296.03/395.13), 23.85% (94.24/395.13) and 1.23% (4.86/395.13), successively; the contributions of edible salt in inland areas, sub-coastal areas and coastal areas were 83.72% (417.64/498.85), 73.05% (280.88/384.50) and 66.83% (280.09/326.33), successively; the contributions of drinking water in sub-coastal areas, coastal areas and inland areas were 1.61% (6.19/384.50) , 1.44% (4.70/326.33) and 0.65% (3.24/498.85) , successively (χ(2) = 7.24, P = 0.032) ; the contribution of laver in coastal areas, sub-coastal areas and inland areas were 22.57% (73.65/326.33), 17.11% (65.79/384.50) and 8.09% (40.36/498.85), successively (χ(2) = 82.17, P < 0.01) ; the contribution of sea fish in coastal areas, sub-coastal areas and inland areas were 2.38% (7.77/326.33), 0.72% (2.77/384.50) and 0.68% (3.39/498.85) (χ(2) = 19.47, P = 0.012).

CONCLUSIONSThe dietary iodine intake of Zhejiang residents was at recommended intake levels; the iodized salt turns out to be the main source, the iodine nutrition level was relatively low in coastal areas of Zhejiang, which the coverage of iodized salt should be improved.

China ; Diet Surveys ; Drinking Water ; Female ; Humans ; Iodine ; analysis ; Male ; Nutritional Status ; Rural Population ; Sodium Chloride, Dietary ; analysis ; Urban Population

OBJECTIVETo observe the influences of seasonal factors on peripheral facial paralysis by acupuncture.

METHODSFour hundred cases of facial paralysis were divided into spring, summer, autumn and winter groups, 100 cases in each group. All these cases were treated by routine puncture. Fengchi (GB 20), Yifeng (TE 17), Qianzheng (Extra), Jiache (ST 6), and Dicang (ST 4), etc. were applied at affect side, once a day. 2 months observation was carried on to compare the clinical therapeutic effects and average courses. The facial symptoms, physical sign and functional activities were taken as observation indexes of therapeutic effect.

RESULTSThe effect rate was 78.0% (78/100) in spring group, 82.0% (82/100) in summer group, 89.0% (89/100) in autumn group and 92.0% (92/100) in winter group; the effect rate in summer or autumn group was superior to those in spring group and in summer group (all P < 0.05); the average course was (47.6 +/- 22.3) days in spring group, (43.7 +/- 18.4) days in summer group, (31.5 +/- 11.3) days in autumn group and (22.6 +/-9.2) days in winter group, indicating the significant differences between groups except that between spring and summer group (all P < 0.01). The cured and markedly effective rate was 80.1% (161/201) for wind cold type, 53.5% (61/114) for wind heat type, and 36.5% (31/85) for damp heat type, indicating that it of wind cold type was superior to that of wind heat type or damp heat type (P < 0.001, P < 0.05).

CONCLUSIONThe syndrome distribution and courses of peripheral facial paralysis are different in different seasons, hence, the diseases should be treated according to attack time and syndromes.

Acupuncture Therapy ; Adolescent ; Adult ; Facial Paralysis ; therapy ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Seasons

OBJECTIVETo investigate the protective effect of reactive oxygen species (ROS) scavenger, N-acetyl-L-cysteine (NAC), against H9c2 cardiomyocytes from injuries induced by chemical hypoxia.

METHODSH9c2 cells were treated with cobalt chloride (CoCl2), a chemical hypoxia-mimetic agent, to establish the chemical hypoxia-induced cardiomyocyte injury model. NAC was added into the cell medium 60 min prior to CoCl2 exposure. The cell viability was evaluated using cell counter kit (CCK-8), and the intercellular ROS level was measured by 2', 7'- dichlorfluorescein-diacetate (DCFH-DA) staining and photofluorography. Mitochondrial membrane potential (MMP) of the cells was observed by Rhodamine123 (Rh123) staining and photofluorography, and the ratio of GSSG/ (GSSG+GSH) was calculated according to detection results of the GSSG kit.

RESULTSExposure of H9c2 cardiomyocytes to 600 micromol/L CoCl2 for 36 h resulted in significantly reduced cell viability. Pretreatment with NAC at the concentrations ranging from 500 to 2000 micromol/L 60 min before CoCl2 exposure dose-dependently inhibited CoCl2-induced H9c2 cell injuries, and obviously increased the cell viability. NAC at 2000 micromol/L obviously inhibited the oxidative stress induced by CoCl2, decreased the ratio of GSSG/(GSSG+GSH), increased ROS level, and antagonized CoCl2-induced inhibition on MMP.

CONCLUSIONNAC offers obvious protective effect on H9c2 cardiomyocytes against injuries induced by chemical hypoxia by decreasing in the ratio of GSSG/(GSSG+GSH) and ROS level and ameliorating MMP.

Animals ; Cell Hypoxia ; drug effects ; Cells, Cultured ; Embryo, Mammalian ; Free Radical Scavengers ; pharmacology ; Myocytes, Cardiac ; drug effects ; metabolism ; pathology ; Oxidative Stress ; drug effects ; Rats ; Reactive Oxygen Species ; metabolism